In vivo detection of serine in the human brain by proton magnetic resonance spectroscopy (1H‐MRS) at 7 Tesla

A single‐voxel proton magnetic resonance spectroscopy (¹H‐MRS) filtering strategy for in vivo detection of serine (Ser) in human brain at 7T is proposed. Spectral difference of coupled resonances arising from different subecho times of triple refocusing at a constant total echo time (TE) was utilized to detect the Ser multiplet and cancel the overlapping creatine (Cr) 3.92‐ppm singlet via difference editing. Dependence of the Ser signal on subecho times was investigated using density‐matrix simulation incorporating the slice‐selective radio frequency (RF) pulses. The simulation indicated that the difference‐edited Ser CH₂ multiplet at ～3.96 ppm is maximized with (TE₁, TE₂, TE₃) = (54, 78, 78) and (36, 152, 22) ms. The edited Ser peak amplitude was estimated, with both numerical and phantom analyses of the performance, as 83% with respect to 90° acquisition for a localized volume, ignoring relaxation effects. From the area ratio of the edited Ser and unedited Cr 3.03‐ppm peaks, assuming identical T₁ and T₂ between Ser and Cr, the Ser‐to‐Cr concentration ratio for the frontal cortex of healthy adults was estimated to be 0.8 ± 0.2 (mean ± SD; N = 6). Magn Reson Med, 2009. © 2009 Wiley‐Liss, Inc.     

Detection of glutamate in the human brain at 3 T using optimized constant time point resolved spectroscopy.

A CT-PRESS sequence was implemented on a 3-T MR scanner and optimized for the detection of the C4 resonance of glutamate. By simulating the sequence using the full density matrix it was found that 121 chemical shift encoding steps in t1 with an increment delta t1 = 1.6 ms were sufficient to separate the glutamate C4 resonance. The simulations also showed that the highest signal-to-noise ratio was achieved at an average echo time of 131 ms. When using an eightfold undersampling scheme in f1 in order to reduce the minimum total measurement time, the average echo time was 139 ms with 17 encoding steps (delta t1 = 12.8 ms). The sequence was tested on phantoms containing solutions of various brain metabolites and on healthy human volunteers. Besides resolving glutamate, other resonances detected in vivo comprised N-acetyl aspartate, total creatine, choline containing compounds, and myo-inositol. However, glutamine resonances could not be resolved due to severe signal overlap from glutamate and N-acetyl aspartate.     

Comparison of spectral fitting methods for overlapping J‐coupled metabolite resonances

There is increasing interest in the use of two‐dimensional J‐resolved spectroscopic acquisition (multiecho) methods for in vivo proton magnetic resonance spectroscopy due to the improved discrimination of overlapping J‐coupled multiplet resonances that is provided. Of particular interest is the potential for discrimination of the overlapping resonances of glutamate and glutamine. In this study, a new time‐domain parametric spectral model that makes use of all available data is described for fitting the complete two‐dimensional multiecho data, and the performance of this method was compared with fitting of one‐dimensional spectra obtained following averaging multiecho data (echo time‐averaged) and single‐echo time PRESS (Point Resolved Spectroscopy) acquired spectra. These methods were compared using data obtained from a phantom containing typical brain metabolites and a human brain. Results indicate that improved performance and accuracy is obtained for the two‐dimensional acquisition and spectral fitting model. Magn Reson Med, 2010. © 2010 Wiley‐Liss, Inc.     

New method for the simultaneous detection of metabolites and water in localized in vivo 1H nuclear magnetic resonance spectroscopy.

A new two-scan method for localized 1H in vivo NMR spectroscopy (MRS) without water suppression (WS) is described. In one of the scans, two chemical shift selective 180 degrees pulses are applied prior to a standard localization sequence to invert all metabolite signals upfield and downfield from water, which remains unaffected. The difference spectrum records the metabolites whereas water and accompanying gradient induced artifacts are widely suppressed. The method was implemented on a 4.7-T system using point resolved spectroscopy with a short echo time of 18 ms. Phantom measurements proved the feasibility of absolute quantification using water as an internal reference. Measurements on healthy rat brain yielded comparable spectrum quality as measurements with water presaturation. The method does not require additional adjustments or sophisticated data postprocessing and scales favorably with increasing B(0) field. Therefore, the method should be useful for 1H MRS without WS. Although the two-step method doubles the minimum total measurement time, it may also be of interest for spectroscopic imaging (SI) without WS, in particular if fast SI techniques are applied.     

Brain metabolites B1‐corrected proton T1 mapping in the rhesus macaque at 3 T

The accuracy of metabolic quantification in MR spectroscopy is limited by the unknown radiofrequency field and T₁. To address both issues in proton (¹H) MR spectroscopy, we obtained radiofrequency field–corrected T₁ maps of N‐acetylaspartate, choline, and creatine in five healthy rhesus macaques at 3 T. For efficient use of the 4 hour experiment, we used a new three‐point protocol that optimizes the precision of T₁ in three‐dimensional ¹H‐MR spectroscopy localization for extensive, ～30%, brain coverage at 0.6 × 0.6 × 0.5 cm³ = 180‐μL spatial resolution. The resulting mean T₁s in 700 voxels were N‐acetylaspartate = 1232 ± 44, creatine = 1238 ± 23 and choline = 1107 ± 56 ms (mean ± standard error of the mean). Their histograms from all 140 voxels in each animal were similar in position and shape, characterized by standard errors of the mean of the full width at half maximum divided by their means of better than 8%. Regional gray matter N‐acetylaspartate, choline, and creatine T₁s (1333 ± 43, 1265 ± 52, and 1131 ± 28 ms) were 5–10% longer than white matter: 1188 ± 34, 1201 ± 24, and 1082 ± 50 ms (statistically significant for the N‐acetylaspartate only), all within 10% of the corresponding published values in the human brain. Magn Reson Med 63:865–871, 2010. © 2010 Wiley‐Liss, Inc.     

Two‐dimensional J‐resolved proton MR spectroscopy and prior knowledge fitting (ProFit) in the frontal and parietal lobes of healthy volunteers: Assessment of metabolite discrimination and general reproducibility

Purpose:

To investigate human brain metabolite discriminability and general measurement reproducibility of two‐dimensional (2D) J‐resolved ¹H MRS and Prior Knowledge Fitting (ProFit).

Materials and Methods:

2D J‐resolved ¹H MRS spectra were acquired from the anterior cingulate cortex (ACC) and the parietal‐occipital cortex (POC) of 10 healthy subjects at a magnetic field strength of 2.9 Tesla. Amplitude correlation matrices were constructed for each subject and brain region to assess metabolite discriminability. ProFit‐estimated metabolite peak areas were normalized to a water reference signal, and intra‐ and inter‐subject reproducibility was evaluated.

Results:

Favorable between‐metabolite correlation coefficients (<20%) were observed for a range of metabolites. Lower correlation coefficients between a given pair of metabolite estimates were consistently observed for POC metabolites. The group mean correlation coefficient existing between glutamate and glutamine was calculated as ?18% and ?13% for ACC and POC, respectively. Most ACC and POC metabolites showed intra‐ and inter‐subject CV values of <15% and <20%, respectively.

Conclusion:

The observed Glu and Gln signal discrimination makes these techniques suitable for investigating a variety of psychiatric disorders. Intra‐ and inter‐subject metabolite level reproducibility was comparable to the existing literature findings. These data serve as a valuable benchmark for assessing future modifications to 2D ¹H MRS data acquisition and ProFit analysis. J. Magn. Reson. Imaging 2013;37:642–651. © 2012 Wiley Periodicals, Inc.

     

Interindividual reproducibility of glutamate quantification using 1.5-T proton magnetic resonance spectroscopy.

The goal of this study was to measure the interindividual reproducibility of glutamate quantification in 1.5-T (1)H MRS of human brains. To determine the effective echo time (TE) for glutamate quantification, spectra from a phantom and 12 participants were obtained with TE = 30, 35, 40, and 144 ms (repetition time (TR) = 2000 ms and volume of interest = 4 cm(3)). The average Cramer-Rao lower bounds for glutamate quantification using LCModel was lowest in two experiments when TE = 40 ms.Twenty-one subjects participated in experiments that measured interindividual reproducibility of glutamate quantification. Spectra were acquired with TR = 6000 ms and TE = 40 ms. Results showed that the coefficients of variance were 11.0 and 13.1% in the anterior cingulate cortex and insula, respectively. This suggests that glutamate can be reproducibly measured from 1.5-T (1)H MRS with long TR, effective TE, and the LCModel.     

Interindividual,repositioning, and time‐of‐day effects on single voxel proton MR spectroscopy of the anterior cingulate cortex

Purpose:

To measure interindividual, repositioning, and time‐of‐day effects of single voxel PRESS (P oint RES olved S pectroscopy) proton magnetic resonance spectroscopy (¹H‐MRS) acquisition of the anterior cingulate cortex (AC) in healthy human subjects.

Materials and Methods:

AC ¹H‐MRS measurements were performed in 15 healthy adult volunteers using a short echo PRESS sequence (GE Healthcare 3 Tesla, TE/TR = 30/2500 ms, 192 acquisitions, 6 cm³ voxels). For each individual, a total of eight spectra were obtained during two identical scanning sessions separated by 3.5 h. In each, two consecutive AC spectra were acquired. After the first two scans, the subject left the scanner, then immediately returned for repositioning and acquisition of two more consecutive spectra. The subject then left the imaging centre to return 3.5 h later for a repeated procedure. Spectroscopic postprocessing was done using LCmodel. Interindividual, repositioning and time‐of‐day effects were measured using restricted maximum likelihood (REML) models of variance components analysis, where response variables were levels of creatine/phosphocreatine (Cr), N‐acetyl‐aspartate (NAA), myo‐inositol (mI), choline (Cho), and the glutamate‐glutamine complex (Glx).

Results:

Interindividual effects were markedly higher than time‐of‐day and repositioning effects for all metabolites.

Conclusion:

Our findings show that ¹H‐MRS measurements of the AC are sensitive to interindividual differences, while time of day and repositioning are markedly less important. J. Magn. Reson. Imaging 2010;32:276–282. © 2010 Wiley‐Liss, Inc.     

Cross‐sectional and longitudinal reproducibility of rhesus macaque brain metabolites: A proton MR spectroscopy study at 3 T

Non‐human primates are often used as preclinical model systems for (mostly diffuse or multi‐focal) neurological disorders and their experimental treatment. Due to cost considerations, such studies frequently utilize non‐destructive imaging modalities, MRI and proton MR spectroscopy (¹H MRS). Cost may explain why the inter‐ and intra‐animal reproducibility of the ¹H MRS observed brain metabolites, are not reported. To this end, we performed test‐retest three‐dimensional brain ¹H MRS in five healthy rhesus macaques at 3 T. Spectra were acquired from 224 isotropic (0.5 cm)³ = 125 μL voxels, over 28 cm³ (～35%) of the brain, then individually phased, frequency aligned and summed into a spectrum representative of the entire volume of interest. This dramatically increases the metabolites' signal‐to‐noise ratios, while maintaining the (narrow) voxel linewidth. The results show that the average N‐acetylaspartate, creatine, choline, and myo‐inositol concentrations in the macaque brain are: 7.7 ± 0.5, 7.0 ± 0.5, 1.2 ± 0.1 and 4.0 ± 0.6 mM/g wet weight (mean ± standard deviation). Their inter‐animal coefficients of variation (CV) are 4%, 4%, 6%, and 15%; and the longitudinal (intra‐animal) CVs are lower still: 4%, 5%, 5%, and 4%, much better than the 22%, 33%, 36%, and 45% intra‐voxel CVs, demonstrating the advantage of the approach and its utility for preclinical studies of diffuse neurological diseases in rhesus macaques. Magn Reson Med, 2011. © 2011 Wiley‐Liss, Inc.     

Measurement of glycine in human prefrontal brain by point‐resolved spectroscopy at 7.0 tesla in vivo

Measurement of glycine in human frontal brain by an optimized point‐resolved spectroscopy sequence at 7 T is reported. Echo time dependencies of the overlapping coupled resonances of myo‐inositol, free choline, and threonine were investigated with density matrix simulations, incorporating the slice‐selective radiofrequency and gradient pulses. The numerical simulations indicated that the selectivity of the 3.55‐ppm glycine singlet is maximized at (TE₁, TE₂) = (101, 51) ms. Phantom experiments indicated that the myo‐inositol peak amplitude between 3.5 and 3.6 ppm is reduced by a factor of 30 following the optimized point‐resolved spectroscopy, as predicted by the simulation. From LCModel analyses, the glycine concentration in the medial prefrontal cortex in healthy adults was estimated, with a mean Cramér‐Rao lower bound of 7 ± 1% (mean ± standard deviation; n = 7), to be 0.8 ± 0.1 mM, with reference to total creatine at 8 mM. Magn Reson Med, 2009. © 2009 Wiley‐Liss, Inc.     

J‐difference editing of gamma‐aminobutyric acid (GABA): Simulated and experimental multiplet patterns

Purpose : To investigate factors that influence the multiplet pattern observed in J‐difference editing of gamma‐aminobutyric acid (GABA). Methods : Density matrix simulations were applied to investigate the shape of the 3 ppm GABA multiplet as a function of the editing sequence's slice‐selective refocusing pulse properties, in particular bandwidth, transition width, and flip angle. For comparison to the calculations, experimental measurements were also made at 3 T on a 10 mM GABA solution using the MEGA‐PRESS sequence at various refocusing pulse flip angles. Results : Good agreement was found between experiments and simulations. The edited multiplet consists of two outer lines of slightly unequal intensity due to strong coupling, and a smaller central line, the result of the unequal J‐couplings between the C4 and C3 protons. The size of the center peak increases with increasing slice‐selective refocusing pulse transition width, and deviation of the flip angle from 180°. Conclusion : The 3 ppm GABA multiplet pattern observed in the MEGA‐PRESS experiment depends quite strongly on the properties of the slice‐selective refocusing pulses used. Under some circumstance, the central peak can be quite large; this does not necessarily indicate inefficient editing, or a subtraction artifact, but should be recognized as a property of the pulse sequence itself. Magn Reson Med 70:1183–1191, 2013. © 2012 Wiley Periodicals, Inc.     

Measurement of transverse relaxation times of J‐coupled metabolites in the human visual cortex at 4 T

Accurate quantification of ¹H NMR spectra often requires knowledge of the relaxation times to correct for signal losses due to relaxation and saturation. In human brain, T₂ values for singlets such as N‐acetylaspartate, creatine, and choline have been reported, but few T₂ values are available for J‐coupled spin systems. The purpose of this study was to measure the T₂ relaxation times of J‐coupled metabolites in the human occipital lobe using the LASER sequence. Spectra were acquired at multiple echo times and were analyzed with an LCModel using basis sets simulated at each echo time. Separate basis spectra were used for resonances of protons belonging to the same molecule but having very different T₂ values (e.g., two separate basis spectra were used for the singlet and multiplet signal in N‐acetylaspartate). The T₂ values for the N‐acetylaspartate multiplet (149 ± 12 ms), glutamate (125 ± 10 ms), myo‐inositol (139 ± 20 ms), and taurine (196 ± 28 ms) were successfully measured in the human visual cortex at 4 T. These measured T₂ relaxation times have enabled the accurate and absolute quantification of cerebral metabolites at longer echo times. Magn Reson Med, 2011. © 2011 Wiley‐Liss, Inc.